OBJECTIVES: Although studies have explored the utilization of healthcare services in patients with restless leg syndrome (RLS), expenditure data are not available. This study assesses the incremental economic burden of illness with RLS. METHODS: A retrospective claims database analysis was conducted using Medstat's MarketScan Commercial Claims and Encounters database from 1999 through 2003. Patients were identified having ≥ 1 RLS diagnosis (ICD-9 333.99) with the earliest claim as the index event. Inclusion criteria required continuous enrollment 6 months pre- and 12 months post-index event. Patients were excluded if they were identified as having Parkinson's disease, post-traumatic neurosurgery, or psychiatric conditions (other than depression and insomnia); or if they had a drug claim in the pre-index period for levodopa, dopamine agonists, opioids, anticonvulsants, amantadine or clonidine. A control group without a diagnosis for RLS and similar inclusion/exclusion criteria as the RLS group was selected using a 1:1 propensity score match. Post-index outcomes included health care utilization and expenditures (2003 dollars), along with multivariate analysis used to determine the incremental economic burden associated with RLS. RESULTS: The RLS group consisted of 2319 patients with an average age of 49.8 years and was 64% female. In the post-index period, RLS patients had higher total expenditures than controls ($8843 vs $4378), with highest costs from outpatient services ($4549 vs $2144, respectively). In the multivariate analysis, the incremental difference in overall expenditures between the RLS cohort ($7257) and controls ($4809) was $2448 (p<0.001). CONCLUSIONS: Expenditures for RLS treated patients are significantly higher when compared to a matched, control cohort of patients, with the highest costs coming from outpatient services. More research is warranted to identify if there are ways to decrease these additional costs while maintaining or improving treatment of patients with RLS.